848 Inhibition of ATR augments immunogenicity in merkel cell carcinoma: A promising approach to address resistance to anti-PD-1 immunotherapy

Abstract

ATR (ataxia telangiectasia and Rad3-related kinase) ensures completion of DNA replication prior to mitosis. It mediates a key survival mechanism for cells with high replication stress (e.g., tumors with high Ki-67 positivity). Surprisingly, after the recent development of potent, selective ATR inhibitors (ATRi), preclinical and clinical studies have shown that ATR inhibition can also reinvigorate anti-tumor immunity and augment immune checkpoint inhibitor (ICI) efficacy. Merkel cell carcinoma (MCC), an immunogenic cancer with Ki-67 positivity in ∼70% of MCC cells, may serve as an appropriate tumor model to test whether ATR inhibition can overcome resistance to PD-1 therapy.